1. Badran HS, Abulnasr KM, Abd El Hameed Nasser S. {{Effect of recurrent otitis media on language profile in children with fragile x syndrome}}. {Clin Med Insights Ear Nose Throat};2013;6:1-7.
OBJECTIVE: Language is almost always affected in fragile X syndrome (FXS), and a delay in language acquisition is one of the first characteristics. The aim of this work was to study the effect of recurrent middle ear infections on the language profile in boys with FXS. STUDY DESIGN: Prospective case series. SETTING: Academic Medical Center. SUBJECTS AND METHODS: The present study was conducted on 30 males, ranging in age from 4-10 years. They were diagnosed as having a full mutation of DNA. The males were divided into two groups: Group A included 15 children with a history of recurrent middle ear infections more than four times per year during the first 4 years of life, and Group B did not have a history of recurrent middle ear infections during the first 4 years of life. Language assessments were done for all participants using the Standardized Arabic Language test. RESULTS: Results showed significant delays in language development in children with FXS. Relative strengths in semantics compared to syntax and pragmatics were observed in all boys. The recurrent ear infections of the boys played an important role in the language development delay. The mean of receptive, expressive, and total language age was better and higher among boys without a history of recurrent middle ear infections compared to boys with recurrent middle ear infections. CONCLUSION: Recurrent otitis media in boys with FXS exacerbates the language problems that exist in this syndrome.
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2. Bakhtiari R, Zurcher NR, Rogier O, Russo B, Hippolyte L, Granziera C, Araabi BN, Nili Ahmadabadi M, Hadjikhani N. {{Differences in white matter reflect atypical developmental trajectory in autism: A Tract-based Spatial Statistics study}}. {Neuroimage Clin};2012;1(1):48-56.
Autism is a neurodevelopmental disorder in which white matter (WM) maturation is affected. We assessed WM integrity in 16 adolescents and 14 adults with high-functioning autism spectrum disorder (ASD) and in matched neurotypical controls (NT) using diffusion weighted imaging and Tract-based Spatial Statistics. Decreased fractional anisotropy (FA) was observed in adolescents with ASD in tracts involved in emotional face processing, language, and executive functioning, including the inferior fronto-occipital fasciculus and the inferior and superior longitudinal fasciculi. Remarkably, no differences in FA were observed between ASD and NT adults. We evaluated the effect of age on WM development across the entire age range. Positive correlations between FA values and age were observed in the right inferior fronto-occipital fasciculus, the left superior longitudinal fasciculus, the corpus callosum, and the cortical spinal tract of ASD participants, but not in NT participants. Our data underscore the dynamic nature of brain development in ASD, showing the presence of an atypical process of WM maturation, that appears to normalize over time and could be at the basis of behavioral improvements often observed in high-functioning autism.
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3. Clery H, Andersson F, Bonnet-Brilhault F, Philippe A, Wicker B, Gomot M. {{fMRI investigation of visual change detection in adults with autism}}. {Neuroimage Clin};2013;2:303-312.
People with autism spectrum disorders (ASD) may show unusual reactions to unexpected changes that appear in their environment. Although several studies have highlighted atypical auditory change processing in ASD, little is known in this disorder about the brain processes involved in visual automatic change detection. The present fMRI study was designed to localize brain activity elicited by unexpected visual changing stimuli in adults with ASD compared to controls. Twelve patients with ASD and 17 healthy adults participated in the experiment in which subjects were presented with a visual oddball sequence while performing a concurrent target detection task. Combined results across participants highlight the involvement of both occipital (BA 18/19) and frontal (BA 6/8) regions during visual change detection. However, adults with ASD display greater activity in the bilateral occipital cortex and in the anterior cingulate cortex (ACC) associated with smaller activation in the superior and middle frontal gyri than controls. A psychophysiological interaction (PPI) analysis was performed with ACC as the seed region and revealed greater functionally connectivity to sensory regions in ASD than in controls, but less connectivity to prefrontal and orbito-frontal cortices. Thus, compared to controls, larger sensory activation associated with reduced frontal activation was seen in ASD during automatic visual change detection. Atypical psychophysiological interactions between frontal and occipital regions were also found, congruent with the idea of atypical connectivity between these regions in ASD. The atypical involvement of the ACC in visual change detection can be related to abnormalities previously observed in the auditory modality, thus supporting the hypothesis of an altered general mechanism of change detection in patients with ASD that would underlie their unusual reaction to change.
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4. Gibbard CR, Ren J, Seunarine KK, Clayden JD, Skuse DH, Clark CA. {{White matter microstructure correlates with autism trait severity in a combined clinical-control sample of high-functioning adults}}. {Neuroimage Clin};2013;3:106-114.
Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in tracts involved in emotion processing in autism spectrum disorder (ASD), but little is known regarding the nature and distribution of WM anomalies in relation to ASD trait severity in adults. Increasing evidence suggests that ASD occurs at the extreme of a distribution of social abilities. We aimed to examine WM microstructure as a potential marker for ASD symptom severity in a combined clinical-neurotypical population. SIENAX was used to estimate whole brain volume. Tract-based spatial statistics (TBSS) was used to provide a voxel-wise comparison of WM microstructure in 50 high-functioning young adults: 25 ASD and 25 neurotypical. The severity of ASD traits was measured by autism quotient (AQ); we examined regressions between DTI markers of WM microstructure and ASD trait severity. Cognitive abilities, measured by intelligence quotient, were well-matched between the groups and were controlled in all analyses. There were no significant group differences in whole brain volume. TBSS showed widespread regions of significantly reduced fractional anisotropy (FA) and increased mean diffusivity (MD) and radial diffusivity (RD) in ASD compared with controls. Linear regression analyses in the combined sample showed that average whole WM skeleton FA was negatively influenced by AQ (p = 0.004), whilst MD and RD were positively related to AQ (p = 0.002; p = 0.001). Regression slopes were similar within both groups and strongest for AQ social, communication and attention switching scores. In conclusion, similar regression characteristics were found between WM microstructure and ASD trait severity in a combined sample of ASD and neurotypical adults. WM anomalies were relatively more severe in the clinically diagnosed sample. Both findings suggest that there is a dimensional relationship between WM microstructure and severity of ASD traits from neurotypical subjects through to clinical ASD, with reduced coherence of WM associated with greater ASD symptoms. General cognitive abilities were independent of the relationship between WM indices and ASD traits.
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5. Hall DA, O’Keefe JA. {{Clinical neurogenetics: fragile x-associated tremor/ataxia syndrome}}. {Neurol Clin};2013 (Nov);31(4):1073-1084.
This article summarizes the clinical findings, genetics, pathophysiology, and treatment of fragile X-associated tremor ataxia syndrome. The disorder occurs from a CGG repeat (55-200) expansion in the fragile X mental retardation 1 gene. It manifests clinically in kinetic tremor, gait ataxia, and executive dysfunction, usually in older men who carry the genetic abnormality. The disorder has distinct radiographic and pathologic findings. Symptomatic treatment is beneficial in some patients. The inheritance is X-linked and family members may be at risk for other fragile X-associated disorders. This information is useful to neurologists, general practitioners, and geneticists.
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6. Harris B, Barton EE, Albert C. {{Evaluating Autism Diagnostic and Screening Tools for Cultural and Linguistic Responsiveness}}. {J Autism Dev Disord};2013 (Nov 2)
While clear guidelines and best practices exist for the assessment of autism spectrum disorders (ASD), little information is available about assessing for ASD in culturally and linguistically diverse (CLD) populations. CLD populations might be misidentified and under-identified with ASD due to the assessment practices that we employ. Four autism diagnostic tools and six autism screeners were selected and evaluated for their cultural and linguistic responsiveness. Although the evaluation of ASD within CLD populations is highly complex, this study identified the need for improved autism assessment tools and practices. Without the appropriate assessment of these populations, CLD children will likely continue to be misidentified (or not identified at all) and will miss crucial intervention opportunities.
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7. Holm RP. {{Patient education: autism is from Mars}}. {S D Med};2013 (Aug);66(8):328.
8. Jiang X, Bollich A, Cox P, Hyder E, James J, Gowani SA, Hadjikhani N, Blanz V, Manoach DS, Barton JJ, Gaillard WD, Riesenhuber M. {{A quantitative link between face discrimination deficits and neuronal selectivity for faces in autism}}. {Neuroimage Clin};2013;2:320-331.
Individuals with Autism Spectrum Disorder (ASD) appear to show a general face discrimination deficit across a range of tasks including social-emotional judgments as well as identification and discrimination. However, functional magnetic resonance imaging (fMRI) studies probing the neural bases of these behavioral differences have produced conflicting results: while some studies have reported reduced or no activity to faces in ASD in the Fusiform Face Area (FFA), a key region in human face processing, others have suggested more typical activation levels, possibly reflecting limitations of conventional fMRI techniques to characterize neuron-level processing. Here, we test the hypotheses that face discrimination abilities are highly heterogeneous in ASD and are mediated by FFA neurons, with differences in face discrimination abilities being quantitatively linked to variations in the estimated selectivity of face neurons in the FFA. Behavioral results revealed a wide distribution of face discrimination performance in ASD, ranging from typical performance to chance level performance. Despite this heterogeneity in perceptual abilities, individual face discrimination performance was well predicted by neural selectivity to faces in the FFA, estimated via both a novel analysis of local voxel-wise correlations, and the more commonly used fMRI rapid adaptation technique. Thus, face processing in ASD appears to rely on the FFA as in typical individuals, differing quantitatively but not qualitatively. These results for the first time mechanistically link variations in the ASD phenotype to specific differences in the typical face processing circuit, identifying promising targets for interventions.
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9. Kikuchi M, Shitamichi K, Yoshimura Y, Ueno S, Hiraishi H, Hirosawa T, Munesue T, Nakatani H, Tsubokawa T, Haruta Y, Oi M, Niida Y, Remijn GB, Takahashi T, Suzuki M, Higashida H, Minabe Y. {{Altered brain connectivity in 3-to 7-year-old children with autism spectrum disorder}}. {Neuroimage Clin};2013;2:394-401.
Autism spectrum disorder (ASD) is often described as a disorder of aberrant neural connectivity and/or aberrant hemispheric lateralization. Although it is important to study the pathophysiology of the developing ASD cortex, the physiological connectivity of the brain in young children with ASD under conscious conditions has not yet been described. Magnetoencephalography (MEG) is a noninvasive brain imaging technique that is practical for use in young children. MEG produces a reference-free signal and is, therefore, an ideal tool for computing the coherence between two distant cortical rhythms. Using a custom child-sized MEG, we recently reported that 5- to 7-year-old children with ASD (n = 26) have inherently different neural pathways than typically developing (TD) children that contribute to their relatively preserved performance of visual tasks. In this study, we performed non-invasive measurements of the brain activity of 70 young children (3-7 years old, of which 18 were aged 3-4 years), a sample consisting of 35 ASD children and 35 TD children. Physiological connectivity and the laterality of physiological connectivity were assessed using intrahemispheric coherence for 9 frequency bands. As a result, significant rightward connectivity between the parietotemporal areas, via gamma band oscillations, was found in the ASD group. As we obtained the non-invasive measurements using a custom child-sized MEG, this is the first study to demonstrate a rightward-lateralized neurophysiological network in conscious young children (including children aged 3-4 years) with ASD.
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10. Lindsay AJ, McCaffrey MW. {{Myosin Va is Required for the Transport of Fragile X Mental Retardation Protein (FMRP) Granules}}. {Biol Cell};2013 (Oct 31)
Background information. Fragile X Mental Retardation Protein (FMRP) is a selective RNA binding protein that functions as a translational inhibitor. It also plays a role in directing the transport of a subset of mRNAs to their site of translation and several recent reports have implicated microtubule motor proteins in the transport of FMRP-messenger ribonucleoprotein (mRNP) granules in neurons. Earlier work reported the association of the actin-based motor protein myosin Va with FMRP granules. Results. Here we follow up on this finding and confirm that myosin Va does in fact associate with FMRP and is required for its correct intracellular localisation. FMRP is concentrated in the perinuclear region of myosin Va-null mouse melanoma cells which contrasts starkly with the evenly distributed punctate pattern observed in wild-type cells. Similarly, overexpression of a dominant-negative mutant of myosin Va results in the accumulation of FMRP in large aggregate-like structures. FRAP experiments demonstrate that FMRP is largely immobile in the absence of myosin Va. Conclusions. Combining this data we propose a model in which myosin Va and kinesin play key roles in the assembly and subsequent transport of FMRP granules along microtubules to the periphery of the cell. Myosin Va captures the complex onto peripheral actin structures and mediates the local delivery of the FMRP granule to the site of mRNA translation. This article is protected by copyright. All rights reserved.
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11. Mehta SQ, Golshani P. {{Clinical neurogenetics: autism spectrum disorders}}. {Neurol Clin};2013 (Nov);31(4):951-968.
Autism spectrum disorders are neurodevelopmental disorders characterized by deficits in social interactions, communication, and repetitive or restricted interests. There is strong evidence that de novo or inherited genetic alterations play a critical role in causing Autism Spectrum Disorders, but non-genetic causes, such as in utero infections, may also play a role. Magnetic resonance imaging based and autopsy studies indicate that early rapid increase in brain size during infancy could underlie the deficits in a large subset of subjects. Clinical studies show benefits for both behavioral and pharmacological treatment strategies. Genotype-specific treatments have the potential for improving outcome in the future.
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12. Posserud MB, Breivik K, Gillberg C, Lundervold AJ. {{ASSERT – The Autism Symptom SElf-ReporT for adolescents and adults: Bifactor analysis and validation in a large adolescent population}}. {Res Dev Disabil};2013 (Oct 28)
With a view to developing a brief screening instrument for autism symptoms in a general population of adolescents, seven items from the Asperger syndrome (and high-functioning autism) diagnostic interview were adapted for use as self-report in an online questionnaire for youths aged 16-19 years (N=10,220). The selected items target lack of social understanding (4 items) and rigid and repetitive behavior and interests (RRBI; 3 items). Factor analyses were performed, and the seven items were also validated against self-reported ASD diagnosis. Best statistical model fit was found for a bifactor model with one general factor and two domain specific factors tied to social difficulties and RRBI. Both the general and the domain specific factors were associated with self-reported ASD diagnoses. The scale (referred to as the Autism Symptom SElf-ReporT for Adolescents and Adults – ASSERT) had good screening properties with a receiver operating curve-area under the curve (ROC-AUC) of 0.87 and a diagnostic odds ratio (DOR) of 15.8. Applying a modified scoring of the scale further improved the screening properties leading to a ROC-AUC of 0.89 and a DOR of 24.9. The ASSERT holds promise as a brief self-report screen for autism symptoms in adolescents, and further studies should explore its usefulness for adults.
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13. Radulescu E, Minati L, Ganeshan B, Harrison NA, Gray MA, Beacher FD, Chatwin C, Young RC, Critchley HD. {{Abnormalities in fronto-striatal connectivity within language networks relate to differences in grey-matter heterogeneity in Asperger syndrome}}. {Neuroimage Clin};2013;2:716-726.
Asperger syndrome (AS) is an Autism Spectrum Disorder (ASD) characterised by qualitative impairment in the development of emotional and social skills with relative preservation of general intellectual abilities, including verbal language. People with AS may nevertheless show atypical language, including rate and frequency of speech production. We previously observed that abnormalities in grey matter homogeneity (measured with texture analysis of structural MR images) in AS individuals when compared with controls are also correlated with the volume of caudate nucleus. Here, we tested a prediction that these distributed abnormalities in grey matter compromise the functional integrity of brain networks supporting verbal communication skills. We therefore measured the functional connectivity between caudate nucleus and cortex during a functional neuroimaging study of language generation (verbal fluency), applying psycho-physiological interaction (PPI) methods to test specifically for differences attributable to grey matter heterogeneity in AS participants. Furthermore, we used dynamic causal modelling (DCM) to characterise the causal directionality of these differences in interregional connectivity during word production. Our results revealed a diagnosis-dependent influence of grey matter heterogeneity on the functional connectivity of the caudate nuclei with right insula/inferior frontal gyrus and anterior cingulate, respectively with the left superior frontal gyrus and right precuneus. Moreover, causal modelling of interactions between inferior frontal gyri, caudate and precuneus, revealed a reliance on bottom-up (stimulus-driven) connections in AS participants that contrasted with a dominance of top-down (cognitive control) connections from prefrontal cortex observed in control participants. These results provide detailed support for previously hypothesised central disconnectivity in ASD and specify discrete brain network targets for diagnosis and therapy in ASD.
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14. Raznahan A, Lenroot R, Thurm A, Gozzi M, Hanley A, Spence SJ, Swedo SE, Giedd JN. {{Mapping cortical anatomy in preschool aged children with autism using surface-based morphometry}}. {Neuroimage Clin};2012;2:111-119.
The challenges of gathering in-vivo measures of brain anatomy from young children have limited the number of independent studies examining neuroanatomical differences between children with autism and typically developing controls (TDCs) during early life, and almost all studies in this critical developmental window focus on global or lobar measures of brain volume. Using a novel cohort of young males with Autistic Disorder and TDCs aged 2 to 5 years, we (i) tested for group differences in traditional measures of global anatomy (total brain, total white, total gray and total cortical volume), and (ii) employed surface-based methods for cortical morphometry to directly measure the two biologically distinct sub-components of cortical volume (CV) at high spatial resolution-cortical thickness (CT) and surface area (SA). While measures of global brain anatomy did not show statistically significant group differences, children with autism showed focal, and CT-specific anatomical disruptions compared to TDCs, consisting of relative cortical thickening in regions with central roles in behavioral regulation, and the processing of language, biological movement and social information. Our findings demonstrate the focal nature of brain involvement in early autism, and provide more spatially and morphometrically specific anatomical phenotypes for subsequent translational study.
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15. Rudie JD, Brown JA, Beck-Pancer D, Hernandez LM, Dennis EL, Thompson PM, Bookheimer SY, Dapretto M. {{Altered functional and structural brain network organization in autism}}. {Neuroimage Clin};2012;2:79-94.
Structural and functional underconnectivity have been reported for multiple brain regions, functional systems, and white matter tracts in individuals with autism spectrum disorders (ASD). Although recent developments in complex network analysis have established that the brain is a modular network exhibiting small-world properties, network level organization has not been carefully examined in ASD. Here we used resting-state functional MRI (n = 42 ASD, n = 37 typically developing; TD) to show that children and adolescents with ASD display reduced short and long-range connectivity within functional systems (i.e., reduced functional integration) and stronger connectivity between functional systems (i.e., reduced functional segregation), particularly in default and higher-order visual regions. Using graph theoretical methods, we show that pairwise group differences in functional connectivity are reflected in network level reductions in modularity and clustering (local efficiency), but shorter characteristic path lengths (higher global efficiency). Structural networks, generated from diffusion tensor MRI derived fiber tracts (n = 51 ASD, n = 43 TD), displayed lower levels of white matter integrity yet higher numbers of fibers. TD and ASD individuals exhibited similar levels of correlation between raw measures of structural and functional connectivity (n = 35 ASD, n = 35 TD). However, a principal component analysis combining structural and functional network properties revealed that the balance of local and global efficiency between structural and functional networks was reduced in ASD, positively correlated with age, and inversely correlated with ASD symptom severity. Overall, our findings suggest that modeling the brain as a complex network will be highly informative in unraveling the biological basis of ASD and other neuropsychiatric disorders.
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16. Smith JM, Xu J, Powell EM. {{Age dependent forebrain structural changes in mice deficient in the autism associated gene Met tyrosine kinase}}. {Neuroimage Clin};2012;1(1):66-74.
The MET tyrosine kinase has been identified as a susceptibility gene in patients with autism spectrum disorders. MET is expressed in the forebrain during prenatal and postnatal development. After birth, MET participates in dendritic outgrowth and circuit formation. Alterations in neuronal development, particularly in the cerebral cortex, may contribute to the pathology of developmental disorders, including autism. Patients with autism can exhibit abnormal cortical volumes and head circumferences. We tested the hypothesis that impaired Met signaling during development alters forebrain structure. We have utilized a conditional mutant mouse line which expresses a kinase-dead Met restricted to the cerebral cortex and hippocampal structures. In these mice, we have used magnetic resonance imaging (MRI) to analyze the structure of the cerebral cortex and related structures across postnatal development. We found that the rostral cortex, caudal hippocampus, dorsal striatum, thalamus, and corpus callosum were all larger in adult, but not juvenile, mutant mice relative to control mice. The specificity of the changes suggests that aberrant expansion of the forebrain is consistent with continued axonal and dendritic growth, potentially leading to improper circuit formation and maintenance.
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17. Snijders TM, Milivojevic B, Kemner C. {{Atypical excitation-inhibition balance in autism captured by the gamma response to contextual modulation}}. {Neuroimage Clin};2013;3:65-72.
Atypical visual perception in people with autism spectrum disorders (ASD) is hypothesized to stem from an imbalance in excitatory and inhibitory processes in the brain. We used neuronal oscillations in the gamma frequency range (30-90 Hz), which emerge from a balanced interaction of excitation and inhibition in the brain, to assess contextual modulation processes in early visual perception. Electroencephalography was recorded in 12 high-functioning adults with ASD and 12 age- and IQ-matched control participants. Oscillations in the gamma frequency range were analyzed in response to stimuli consisting of small line-like elements. Orientation-specific contextual modulation was manipulated by parametrically increasing the amount of homogeneously oriented elements in the stimuli. The stimuli elicited a strong steady-state gamma response around the refresh-rate of 60 Hz, which was larger for controls than for participants with ASD. The amount of orientation homogeneity (contextual modulation) influenced the gamma response in control subjects, while for subjects with ASD this was not the case. The atypical steady-state gamma response to contextual modulation in subjects with ASD may capture the link between an imbalance in excitatory and inhibitory neuronal processing and atypical visual processing in ASD.
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18. Srinivasan SM, Lynch KA, Bubela DJ, Gifford TD, Bhat AN. {{Effect of interactions between a child and a robot on the imitation and praxis performance of typically devloping children and a child with autism: a preliminary study}}. {Percept Mot Skills};2013 (Jun);116(3):885-904.
Interactions between a robot and a child (robot-child interactions) provide a unique context to engage children in whole body movements through a reciprocal imitation game. The effects of a novel, 8-session, robot-child interaction protocol on the imitation and praxis skills of 15 typically developing children and one child with autism between 4 and 7 years of age were examined. A quasi-experimental observational comparison of pretest and posttest performance was conducted. A task-specific robot imitation test and a standardized praxis measure were coded for changes in imitation and praxis errors at pretest and posttest. All children showed improvements in task-specific imitation and generalized praxis. Interpretation is limited by the lack of a control group. These findings serve as a foundation for further investigation of robot-child interactions as a potential training tool for children with dyspraxia.
19. Ung D, Wood JJ, Ehrenreich-May J, Arnold EB, Fuji C, Renno P, Murphy TK, Lewin AB, Mutch PJ, Storch EA. {{Clinical characteristics of high-functioning youth with autism spectrum disorder and anxiety}}. {Neuropsychiatry (London)};2013 (Apr);3(2)
AIM & METHODS: Clinical characteristics were examined in 108 high-functioning youth (children with a full IQ scale of at least 70) with an autism spectrum disorder (ASD; aged 7-15 years) who were presenting for inclusion in one of four clinical trials examining the efficacy of cognitive behavioral therapy in youth with ASD and anxiety. RESULTS: We present baseline characteristics of this cohort, including prevalence rates of anxiety and comorbid disorders, and correlates of anxiety (e.g., comorbid diagnoses, impairment, anxiety severity and mental health services received) as a function of age and ASD diagnosis in treatment-seeking youth. Primary anxiety disorders were: 41.7% (n = 45) social phobia, 25.9% (n = 28) generalized anxiety disorder, 15.7% (n = 17) separation anxiety disorder, 12.0% (n = 13) obsessive-compulsive disorder and 4.6% (n = 5) specific phobia. Overall, 91.6% of participants (n = 99) met criteria for two or more anxiety disorders. Parents reported considerable functional impairment as measured by the Columbia Impairment Scale and anxiety severity as measured by the Pediatric Anxiety Rating Scale; this did not statistically differ as a function of ASD diagnosis or age. Anxiety severity, the number of comorbid anxiety diagnoses and total comorbid diagnoses were directly associated with parent-reported child impairment. Youth with ASD and anxiety present as a heterogeneous cohort with significant impairments and complex diagnostic presentations. CONCLUSION: These data provide information about the nature of anxiety in youth with ASD, which may foster the development of tailored treatment protocols.
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20. Wiggins JL, Peltier SJ, Bedoyan JK, Carrasco M, Welsh RC, Martin DM, Lord C, Monk CS. {{The impact of serotonin transporter genotype on default network connectivity in children and adolescents with autism spectrum disorders}}. {Neuroimage Clin};2012;2:17-24.
Compared to healthy controls, individuals with autism spectrum disorders (ASD) have weaker posterior-anterior connectivity that strengthens less with age within the default network, a set of brain structures connected in the absence of a task and likely involved in social function. The serotonin transporter-linked polymorphic region (5-HTTLPR) genotypes that result in lowered serotonin transporter expression are associated with social impairment in ASD. Additionally, in healthy controls, low expressing 5-HTTLPR genotypes are associated with weaker default network connectivity. However, in ASD, the effect of 5-HTTLPR on the default network is unknown. We hypothesized that 5-HTTLPR’s influence on posterior-anterior default network connectivity strength as well as on age-related changes in connectivity differs in the ASD group versus controls. Youth with ASD and healthy controls, ages 8-19, underwent a resting fMRI acquisition. Connectivity was calculated by correlating the posterior hub of the default network with all voxels. Triallelic genotype was assessed via PCR and Sanger sequencing. A genotype-by-diagnosis interaction significantly predicted posterior-anterior connectivity, such that low expressing genotypes (S/S, S/LG, LG/LG) were associated with stronger connectivity than high expressing genotypes (LA/LA, S/LA, LA/LG) in the ASD group, but the converse was true for controls. Also, youth with ASD and low expressing genotypes had greater age-related increases in connectivity values compared to those with high expressing genotypes and controls in either genotype group. Our findings suggest that the cascade of events from genetic variation to brain function differs in ASD. Also, low expressing genotypes may represent a subtype within ASD.
